Influence of maternal HIV-1 infection on the vertical transfer of epstein barr virus specific immunoglobuling

Abstract

ABSTRACT: More than 35% of infants residing in Chulaimbo regions are infected with Epstein–Barr virus (EBV) by six months of age, typically when maternal antibodies are expected to provide protection to the infants before they develop their own denovo antibodies. It has been reported that maternal immunoglobulin G (IgG) antibodies get transferred to the fetus from the second week of gestation and reach maximum levels by the third trimester. Transplacental transfer of these antibodies may be affected by several factors including: maternal infections such as human immunodeficiency virus (HIV-1). Inefficient transfer of EBV specific IgG during pregnancy may later predispose infants to early age of EBV infection. Therefore, this study determined the influence of maternal HIV-1 infection on the transfer of EBV specific antibodies to their neonates. The study specifically determined total IgG antibody levels in HIV-1 infected mothers, HIV-1 uninfected mothers and their corresponding neonates; determined levels of EBV specific IgG antibodies in HIV-1 infected mothers, HIV-1 uninfected mothers and their corresponding neonates and determined EBV specific IgG subclasses levels in HIV-1 infected mothers, HIV-1 uninfected mothers and their corresponding neonates. In this cross-sectional study, thirty-five HIV infected and thirty-five HIV uninfected pregnant women were randomly selected and recruited from Chulaimbo Sub-County Hospital and followed through pregnancy to delivery. The levels of total IgG, EBV specific IgG and IgG sub-classes in maternal venous blood and in cord blood was quantified using Enzyme-linked immunosorbent assay (ELISA). Total IgG antibody levels were compared between mothers and between neonates using Mann Whitney U test. Mann Whitney U test was also used to compare the median levels of EBV specific IgG antibodies and IgG subclasses between HIV infected and HIV uninfected mothers as well as between HIV exposed and HIV non-exposed neonates. Wilcoxon matched pairs test was used to compare EBV specific antibody levels in maternal and their corresponding neonates. The levels of total IgG were significantly higher in HIV infected mothers than HIV uninfected mothers and between HIV exposed neonates compared to HIV unexposed neonates (p=0.0001). HIV-1 exposed neonates had significantly lower levels of anti- EBV nuclear antigen (EBNA1) antibodies than in HIV-1 non-exposed neonates (p=0.0045). In utero exposure to HIV resulted in reduction in vertical transfer of; anti-EBNA1, anti-viral capsid antigen (VCA) IgG1 antibodies and anti-EBNA1 IgG1 antibodies (1.1%, 18.8% and 27.8% respectively). Levels of IgG1 and IgG4 against both VCA and EBNA1 were significantly higher in HIV infected mothers compared to HIV uninfected mothers (p=0.0357, 0.0072, 0.0458 and 0.0015 respectively). In addition, the levels of IgG3 against EBNA1 only were significantly high in HIV-infected mothers. These data suggest that, maternal HIV-1 infection contribute to impairment of transplacental transfer of EBV specific antibodies which may in turn lead to the early EBV infection in this high-risk population. These results are useful in development of EBV specific preventive and therapeutic measures tailored to children born to HIV infected mothers.